Lecture 14 Carbohydrate recognitionin cell adhesion and signalling
Lecture'14'Carbohydrate'recogni4on' in'cell'adhesion'and'signalling
Learning objects. The classification of sugar-binding proteins basedon structures of carbohydrate-recognitiondomains The roles of mannose-binding protein and otherC-type lectins in innate immunity· How the selectins function as cell-adhesionmolecules The adhesion and signalling functions of siglecs intheimmunesystem: How galectins modulate adhesion and signallingin lymphocytes（淋巴细胞)and other cells
Learning'objects' • The'classifica4on'of'sugar;binding'proteins'based' on'structures'of'carbohydrate;recogni4on' domains' • The'roles'of'mannose;binding'protein'and'other' C;type'lec4ns in'innate'immunity' • How'the'selec4ns'func4on'as'cell;adhesion' molecules' • The'adhesion'and'signalling'func4ons'of'siglecs in' the'immune'system' • How'galec4ns modulate'adhesion'and'signalling in'lymphocytes'(淋巴细胞)'and'other'cells
Lectins serve asreceptorsforspecificglycansrecognizeforeigncell surfaces mediate or modulate immune responses topathogens: bind to endogenous carbohydrates: mediate adhesion or signalling events at thecellsurface
• Lec4ns serve'as'receptors'for'specific'glycans'' • recognize'foreign'cell'surfaces'' • mediate'or'modulate'immune'responses'to' pathogens'' • bind'to'endogenous'carbohydrates'' • mediate'adhesion'or'signalling'events'at'the' cell'surface
1 Animal lectins can be classifiedaccording to their structures
1 Animal lectins can be classified according to their structures
Carbohydrate-recognitiondomains(CRD)· CRDs are responsible for the recognition functionsof the lectins. Other domains in the lectins mediate subseguentresponses· Different types of CRD have distinct ancestry (家谱)and different polypeptide foldsThe overall folds of CRDs are determined byconserved residues that are characteristic of eachfamilyofCRDsThese residues form the hydrophobic core and insome cases disulphide bonds and binding sitesfordivalent cations
• CRDs'are'responsible'for'the'recogni4on'func4ons' of'the'lec4ns • Other'domains'in'the'lec4ns'mediate'subsequent' responses'' • Different'types'of'CRD'have'dis4nct'ancestry'(家谱)' and'different'polypep4de'folds' • The'overall'folds'of'CRDs'are'determined'by' conserved'residues'that'are'characteris4c'of'each' family'of'CRDs' • These'residues'form'the'hydrophobic'core'and'in' some'cases'disulphide'bonds'and'binding'sites'for' divalent'ca4ons Carbohydrate-recognition domains (CRD)
TypeStructureTypical ligandsExamplesoffunctioncalnexinβ-SandwichGlc,MangProtein sorting in the ER(内质网）MangM-typeα-Helical barrelER-associatedproteindegradationL-typeβ-SandwichMans-9Protein sorting in the ERMan6-Pp-typeUniqueβ-richstructureProtein sorting post-GolgiC-typeVariousUnique mixed α/βCell adhesion (selectins);structureglycoproteinclearance;innateimmunity(collectins)Galectinsβ-Sandwichβ-GalactosidesGlycan cross-linking intheextracellularmatrixI-typeSialicacidImmunoglobulinCell adhesion(siglecs)superfamilyβ-TrefoilVariousR-typeEnzyme targeting;glycoproteinhormoneturnover
Type% Structure% Typical%ligands% Examples%of%func7on% calnexin β;Sandwich' Glc1Man9' Protein'sor4ng'in'the'ER (内质网) M;type' α;Helical'barrel' Man8' ER;associated'protein' degrada4on' L;type' β;Sandwich' Man5;9 Protein'sor4ng'in'the'ER P;type' Unique'β;rich'structure' Man6;P' Protein'sor4ng'post; Golgi' C;type' Unique'mixed'α/β structure' Various' Cell'adhesion'(selec4ns);' glycoprotein'clearance;' innate'immunity' (collec4ns)' Galec4ns β;Sandwich' β;Galactosides Glycan'cross;linking'in' the'extracellular'matrix' I;type' Immunoglobulin' superfamily' Sialic'acid' Cell'adhesion'(siglecs)' R;type' β;Trefoil' Various' Enzyme'targe4ng;' glycoprotein'hormone' turnover
2 Mannose-binding protein (MBP) is ahost defence molecule that initiates thelectinpathway of complement activation(补体激活）
2 Mannose-binding protein (MBP) is a host defence molecule that initiates the lectin pathway of complement activation (补体激活)
innateimmune system（先天性免疫系统): Distinguished from adaptive immune system（获得性免疫系统）. cells of the innate system recognize andrespond to pathogens in a generic way provide immediate defense against infection,and are found in all classes of plant andanimal life
innate'immune'system'(先天性免疫系统)' • Dis4nguished'from'adap4ve'immune'system' (获得性免疫系统)' • cells'of'the'innate'system'recognize'and' respond'to'pathogens'in'a'generic'way' • provide'immediate'defense'against'infec4on,' and'are'found'in'all'classes'of'plant'and' animal'life
The complement system(补体系统）helpsor “complements” the ability ofantibodies and phagocytic cells（噬菌细胞) to clear pathogens from anorganism.It is part of the innate immune systemand does not change over the course ofan individual's lifetime
The complement system(补体系统) helps or “complements” the ability of antibodies and phagocytic cells (噬菌细 胞) to clear pathogens from an organism. It is part of the innate immune system and does not change over the course of an individual's lifetime
MBP: Binds to carbohydrate structure on thesurface of microorganisms. Using the ability to distinguish exogenousstructures from mammalian glycans. To provide a mechanism for identification andneutralization of pathogen· Circulates constitutively in the blood streamprovides a type of innate immune response
MBP' • Binds'to'carbohydrate'structure'on'the' surface'of'microorganisms' • Using'the'ability'to'dis4nguish'exogenous' structures'from'mammalian'glycans'' • To'provide'a'mechanism'for'iden4fica4on'and' neutraliza4on'of'pathogen' • Circulates'cons4tu4vely'in'the'blood'stream' provides'a'type'of'innate'immune'response